Researchers investigating an experimental malaria immunization are moving it into a large phase III trial in response to recent positive results.

"We are closer than ever before to having a malaria vaccine," said Dr. Christian Loucq, director of the PATH Malaria Vaccine Initiative. "The world urgently needs a safe and effective vaccine. Even a partially effective vaccine has the potential to save hundreds of thousands of lives each year."

Data from phase II projects investigating the RTS,S/AS01E and the RTS,S/AS02D malaria vaccines were published in the Dec. 11, 2008, New England Journal of Medicine and presented at last month's American Society of Tropical Medicine and Hygiene meeting in New Orleans.

These two-shot formulas contain the same antigen but have different adjuvants.

One study randomized 894 infants and toddlers in Kenya and Tanzania to receive either RTS,S/AS01E or rabies shots. The RTS,S/AS01E vaccine reduced the incidence of illness caused by the malaria parasite by 53% over eight months. Those receiving the investigation product also experienced fewer serious adverse events than did those who received the rabies vaccine.

A second study randomized 340 infants in Tanzania to receive either three doses of RTS,S/AS02D or the hepatitis B vaccination, in conjunction with the usual immunization schedule. The RTS,S/AS02D vaccine reduced the risk of being infected with the malaria parasite by slightly more than 65% over a six-month period. Also, it did not interfere with the effect of the other vaccines.

"These results are very exciting and give me renewed hope of having a malaria vaccine in the not-too-distant future," said Dr. Salim Abdulla, lead author on the second paper and head of the Bagamoyo Branch of the Ifakara Health Institute in Bagamoyo, Tanzania.

Multicenter phase III efficacy trials are expected to start early this year, pending approval by national regulatory agencies and ethics committees.

The print version of this content appeared in the Jan. 5, 2009 issue of American Medical News.

Denise Bunning had no idea that switching her 6½-month-old son from breast milk to a milk-based formula would threaten his life. But Bryan's first sips proved perilous. His lips and tongue swelled, and his eyes rolled back. "I didn't know what was happening," says Bunning, who, with her husband, David, co-founded the Food Allergy Project in Chicago.

Bryan was diagnosed with life-threatening allergies to milk, eggs, tree nuts and sesame seeds. So when their second son, Daniel, was born, the Bunnings took precautions. Still, at 9 months he also had an anaphylactic reaction after a babysitter inadvertently put a milk-soiled bib around his neck. "His allergies are even worse," she says. "In addition to milk, eggs and tree nuts, he is also allergic to beef, turkey and shellfish."

For reasons scientists cannot yet explain, food allergies are increasing, especially among children. According to the Centers for Disease Control and Prevention, the number of food or digestive allergies in those younger than 18 increased 18% in the last decade. In an October 2008 report, the CDC estimated that 3 million U.S. children and teenagers have a food or digestive allergy, compared with just more than 2.3 million in 1997. And more than 9,000 annual pediatric hospital discharges had a food allergy diagnosis.

But the problem goes beyond children -- 1% to 2% of adults have food allergies, which can emerge at all ages for many reasons. Recent studies focus on pediatric patients, but many of the themes are applicable. The key differences involve patterns. For instance, the most common food allergies among adults are shellfish, fish, peanuts, tree nuts and eggs. For kids, it's cow's milk, eggs, peanuts, tree nuts and sesame seeds. Also, while children often outgrow these issues, adults do not.

"There's an epidemic of allergies," says Clifford Bassett, MD, assistant clinical professor of medicine at Long Island College Hospital in Brooklyn and medical director of Allergy and Asthma Care of New York. He also is the vice president of public education for the American Academy of Allergy, Asthma & Immunology. "Today, one in 26 children has a food allergy, up from one in 30 in 1997."

According to the CDC, eight foods -- milk, eggs, peanuts, tree nuts, fish, shellfish, soy and wheat -- account for 90% of allergies. With reactions ranging from tingling around the mouth and lips to hives and even death, management can be challenging. "There are 200 fatalities each year from food allergies. This is an important problem," Dr. Bassett says. "There needs to be more education of physicians and patients. Parents need a plan, an EpiPen, and we need to teach them how to be label detectives."

The hardest part, says the Food Allergy Project's David Bunning, is unexpected exposure. It can be a bite of a cookie, peanut shell dust at a ballgame or a dairy-coated pill. But all can lead to an anaphylactic reaction or even death. "Avoidance becomes all-encompassing," he says. "And regardless of how careful we are, every year or so we have an accidental cross-contamination."

A little bit of dirt and other theories

Corresponding to this increase in food allergies is an increase in allergies overall, says David L. Rosenstreich, MD, director of the division of allergy and immunology at Montefiore Medical Center in New York. "There is clearly more asthma, there is clearly more rhinitis. Why is this happening?"

While possible explanations abound, not enough evidence exists to pinpoint a cause, says Jonathan Field, MD, director of the pediatric allergies and asthma clinic at New York University's Langone Medical Center, in Bellevue.

8 foods account for 90% of food allergies.

Food-specific theories question if our diets have changed in subtle ways, maybe with nutrients that push more toward allergic responses. Others note that eating more or maybe even less of specific allergenic foods is to blame. Some theories even center on how a food is processed. For example, maybe roasting peanuts makes them more allergenic than boiling or frying, a common preparation in Asia, where peanuts are frequently eaten but peanut allergy rates appear lower, says Scott H. Sicherer, MD. He is associate professor of pediatrics at the Jaffe Food Allergy Institute, Mount Sinai School of Medicine in New York. Other theories blame a lack of sun exposure and decreased vitamin D, he adds, noting data indicating that more people with anaphylaxis live in northern climates.

The hygiene theory also is popular. Some experts say society is too clean, keeping kids' immune systems from maturing as they did in the past. "The hygiene hypothesis says that we are oversanitizing the early environment of the child," Dr. Bassett says. "The immune system has less exposure to dirt, germs and bugs."

In support of this perspective, researchers point to Eastern Germany before the fall of the Berlin Wall. "They had much lower rates of allergy," Dr. Field says. "As they were westernized, they had more."

Maybe a little dirt is not so bad, Dr. Rosenstreich says. "In the farm studies, children who live on farms in close proximity to animals and are exposed to endotoxins have fewer allergies. And it looks like a pet in the home in the first year of life may well protect children from asthma. This is the opposite of what we've been teaching."

According to a release by the American Academy of Allergy, Asthma & Immunology, new research casts doubt on food avoidance recommendations -- specifically, that infants and new mothers avoid eating peanuts. The study, published in the November 2008 Journal of Allergy and Clinical Immunology, found that children who avoided peanuts in infancy and early childhood were 10 times as likely to develop peanut allergy as those who were exposed to them.

Researchers measured the incidence of peanut allergy in 8,600 Jewish school-age children in the United Kingdom and Israel. Prevalence of the allergy in the U.K. was estimated at 1.85% versus 0.17% in Israel. "Actually, peanut is eaten at an earlier age in Israel, lending argument to the idea that perhaps earlier exposure is not a problem," Dr. Sicherer says.

Food or digestive allergies in children increased 18% in the last decade.

Nonetheless, the AAAAI cautions that, although the results are promising, they shouldn't translate to changes in treatment just yet. "While this study's findings provide optimism for prevention of peanut allergy in the future, randomized, controlled trials are needed to verify that early introduction of peanut is indeed effective," says Jacqueline A. Pongracic, MD, vice chair of the allergy academy's Adverse Reactions to Foods Committee.

Similarly, a study published in the Oct. 28, 2008, Journal of Allergy and Clinical Immunology explored milk exposure and milk allergies. Investigators from Johns Hopkins Children's Center and Duke University found that giving children increasingly higher doses of milk over time may ease milk allergy. "They were able to greatly increase tolerance to milk," Dr. Rosenstreich says. "Total avoidance may also be a mistake."

In another twist, a recent study found evidence that early cat ownership may help protect young children against developing asthma symptoms. The research was conducted by scientists at the Columbia Center for Children's Environmental Health at Columbia's Mailman School of Public Health, in New York.

Education and research

Clinical signs of food allergy often are confused with other reactions, most commonly intolerance. "The question is are they truly food allergic," says Jonathan Bernstein, MD, professor of medicine in the division of immunology and allergy, Dept. of Internal Medicine at the University of Cincinnati College of Medicine.

Guidelines published in the March 2007 Annals of Allergy, Asthma & Immunology help clarify food allergy diagnosis and management, which begin with a detailed history, confirmatory testing and education about day-to-day living. The diagnostic gold standard is the double-blind, placebo-controlled food challenge. "For children, many food allergies are outgrown, so repeated evaluations are needed," Dr. Sicherer says.

In a study in the September 2008 BMC Medical Education, however, researchers found that primary care physicians are not trained adequately in food allergy management. This survey and others found a majority of respondents were unable to identify risk factors for anaphylaxis.

"Our previous studies also showed that too many doctors did not know, for example, exactly how to teach people how and when to use self-injectable epinephrine," Dr. Sicherer says. "We were funded by the U.S. Dept. of Agriculture to create an educational program for doctors who care for teenagers and adults with food allergy. The program focuses on nuances. ... There are a lot of things the doctor must keep up on, including new labeling laws, for example."

Dr. Bernstein says it's important for primary care physicians to ask patients what happens when they eat the suspected food. "We don't want to create hysteria," he says. "It's important to find out if it is an allergy, and sending someone for a consult to clarify is not bailing from your patient."

The print version of this content appeared in the Jan. 5, 2009 issue of American Medical News.

Washington -- Declining incidence and death rates for some of the nation's most common cancers mean physicians can take a deep breath, pat themselves on the back and keep up the good work.

It looks like increasing screening rates and encouraging patients to toss out the cigarettes are effective strategies, but more patients should be following through on both, according to the "Annual Report to the Nation on the Status of Cancer, 1975-2005."

The report, published online Nov. 25, 2008, and printed a week later in the Journal of the National Cancer Institute, found that, for the first time since the report was issued in 1998, trend lines went down for all cancers combined. These declines were driven by drops in some of the most common types of cancers -- including breast and colorectal, for which there are effective screening tests.

The report shows that incidence rates for all cancers decreased 0.8% per year from 1999 through 2005 for both sexes. Incidence rates decreased 1.8% per year for men from 2001 through 2005, and 0.6% per year for women from 1998 through 2005.

Death rates for all cancers also decreased an average of 1.8% per year from 2002 through 2005.

61% of women older than 40 get a mammogram yearly; compared with 32% of women without a medical home.

Celebration surrounded this good news, but so did a degree of wariness. "The drop in incidence seen in this year's annual report is something we've been waiting to see for a long time," said Otis W. Brawley, MD, chief medical officer of the American Cancer Society, one of the groups responsible for the report. The others were the Centers for Disease Control and Prevention, the National Cancer Institute and the North American Assn. of Central Cancer Registries. "[But] we have to be somewhat cautious about how we interpret it because changes in incidence can be caused not only by reductions in risk factors for cancer, but also by changes in screening practices."

For example, the reasons behind the 2.2% decline per year in breast cancer incidence rates from 1999 through 2005 could be good or bad. On the positive side, some speculate the drop is due to the rapid discontinuation of hormone replacement therapy. Conversely, though, that reduction could be an offshoot of the recent drop in the number of screening mammograms, meaning the cancer may be evading detection. Time and a watch over the breast cancer death rate will tell which it is. "We need to keep an eye on this," said Therese Bevers, MD, medical director for Clinical Cancer Prevention at the University of Texas M.D. Anderson Cancer Center in Houston.

"The bad news is that after going up for many years and then leveling off, mammogram screening has dropped since 2003," said Elizabeth Fontham, MPH, DrPH, president of the American Cancer Society.

The importance of a medical home

She urged physicians to continue to refer women for mammograms. These referrals play a crucial role. While 61% of women older than 40 receive them, that rate drops to 32% among those without a usual source of medical care, said Fontham, who also is dean of the Louisiana State University Health Sciences Center's School of Public Health. "That to me is a huge red flag about the importance of a medical home and continuity of care. The primary care physician is key to getting appropriate screening."

In addition, physicians should make sure patients are following through on these tests, said Dr. Bevers. Many radiology facilities no longer offer mammograms because of low or nonexistent profit margins and high liability risks. "Women may call, find that the facility isn't doing it anymore, may not find another facility and miss their mammogram."

Physicians also should continue to encourage patients to receive screening colonoscopies, added Dr. Bevers. Their benefit may be seen in the dropping incidence rate for colorectal cancer -- a decline of 2.8% per year among men and 2.2% per year among women from 1998 to 2005.

"This report demonstrates the importance of colorectal cancer screening beginning at age 50," said John L. Petrini, MD, president of the American Society for Gastrointestinal Endoscopy. "While we are encouraged by this excellent news, far too few people are getting screened."

As is the case for mammograms, a medical home is an important driver for colonoscopies, said Fontham. Only about 26% of people without a medical home receive them, compared with 56% of those referred by their primary care physicians, she added.

The report, which also includes a section on tobacco use and lung cancer, found substantial differences in death rates by state and geographic region. Lung cancer deaths among men declined an average of 2.8% per year from 1996 through 2005 in California, which enacted a smoking ban in 1998. This amount was more than twice the drop seen in Midwest and Southern states that have no bans, according to the report.

Tobacco control remains the only way to continue to achieve these reductions, noted Dr. Bevers. Although no lung cancer screening tests currently exist, results from ongoing trials are expected in about a year.

Meanwhile, counseling patients to quit smoking and offering them assistance has been found to work, said Dr. Bevers. Many medical groups, including the American Medical Association, favor aggressively pursuing all avenues of educating patients and the general public on tobacco's harms and offering patients counseling and medications to help.

Dr. Bevers suggested doctors get involved in efforts to enact smoking bans. "In Texas, we tried it in the last legislative session." Although that effort failed, "we will try again."

The print version of this content appeared in the Jan. 5, 2009 issue of American Medical News.

Washington -- "Keep moving to help ward off cancer" is a message that seems to be picking up momentum.

Evidence has built in recent years that risk for breast cancer, in particular, increases with a sedentary lifestyle, said several researchers at the American Assn. for Cancer Research's International Conference on Frontiers in Cancer Prevention Research. The meeting was held Nov. 16-19 in Oxon Hill, Md., outside Washington, D.C.

Numerous studies have shown that "fitness" and "fatness" both are important cancer risk factors, said Anne McTiernan, MD, PhD, director of the Fred Hutchinson Cancer Research Center's Prevention Center in Seattle.

With national obesity rates continuing to rise, Dr. McTiernan warned that breast cancer incidence could increase and that the prognosis for diagnosed cases could worsen. Several supporting studies, including findings from the World Health Organization's International Agency for Research on Cancer, conclude that excess weight and lack of physical activity account for one-quarter to one-third of breast cancer cases.

Dr. McTiernan cited research findings that breast cancer patients who are overweight and obese have poorer survival rates and increased chances of cancer recurrence compared with patients who weigh less.

Except for non-melanoma skin cancer, breast cancer is the most common form of cancer in U.S. women, according to the Centers for Disease Control and Prevention. The National Cancer Institute estimates that 182,460 women will be diagnosed with breast cancer this year, and 40,480 will die of it.

Several researchers explored ways to reduce those numbers. Findings from one study showed that regular physical activity can lower a woman's overall risk of cancer, but only if she also gets a good night's sleep.

James McClain, PhD, a cancer prevention fellow at the National Cancer Institute, found that although increased physical activity is associated with reduced cancer risk, including that of breast and colon cancers, additional research has shown that reduced sleep -- fewer than seven hours -- increases the risk of breast cancer.

McClain and colleagues followed nearly 6,000 women who enrolled in a 1998 study in Washington County, Md. All were cancer-free at the study's start. During the next 10 years, 604 cases of cancer were diagnosed, including 186 breast cancer cases.

The role of sleep

The researchers found that women who exercised the most had a greater reduction in cancer risk than did those who reported low exercise levels. While they also found that sleep was not independently associated with cancer risk, it does play a surprisingly large role. In fact, women who were the most active and were younger than 65 but reported sleeping less than seven hours a night had an increased risk of all types of cancer.

"These findings highlight the importance of being physically active with respect to reducing cancer risk and suggest that sleep, specifically duration, is also important. ... This interesting finding needs to be confirmed in subsequent studies," McClain said.

A study from Duke University's Center for Population Health and Aging in North Carolina also examined lifestyle factors and cancer risk, but focused on those older than 65. Among its conclusions: "Moderate physical activities are capable of decreasing cancer risk," said lead researcher Igor Akushevich, PhD, senior research scientist at the center.

The Duke researchers used data from the National Long Term Care Survey; Medicare; and the Surveillance, Epidemiology and End Results Program.

An antibiotic regimen four months long results in more patients with latent tuberculosis taking all their pills than does the more common nine-month approach, according to a study in a November Annals of Internal Medicine (www.annals.org/cgi/content/abstract/149/10/689/). Trials with more participants now are needed to determine if this shorter course is as effective at eradicating the bacteria.

"It's about just trying to get people to finish treatment," said Dr. Dick Menzies, lead author and director of the respiratory division at McGill University in Montreal. "If you prescribe an antibiotic for a week, a lot of people don't finish. When I tell people they need nine months, their face falls and they're looking around trying to get away. It seems impossible."

Researchers randomized 847 latent TB patients in Canada, Brazil and Saudi Arabia to either four months of daily rifampin or nine months of daily isoniazid. Both medicines were taken daily and are guideline-recommended regimens, although the longer course is preferred. Of the 422 patients randomized to isoniazid, 17 developed serious adverse events, compared with seven of the 418 on rifampin. Also, 60% of those taking isoniazid completed treatment, while 78% on rifampin finished the course.

Experts say the data indicate the need to determine if the shorter regimen works as well as longer ones in eradicating this infection, and the study authors are now seeking funding to do so. They also are analyzing how the two regimens compare on cost.

Scientists have long hunted for antibiotic regimens that are easier to take, because evidence suggests that fewer than half of patients comply with latent TB treatment. The hope is that shorter regimens with fewer adverse events will make it more likely that the course will be completed and that the spread of this infection, which already has decreased significantly, will diminish further.

According to an October Centers for Disease Control and Prevention tuberculosis report, the rate of active TB was 4.4 per 100,000 in 2007 -- the lowest rate since 1953, when reporting began (www.cdc.gov/tb). The agency also is running its own trial comparing three months of weekly rifapentine combined with daily isoniazid to nine months of daily isoniazid by itself. Those results are expected in 2010.

The American Medical Association supports legislation leading to increased resources for TB control in the U.S. and abroad.